Tissue engineering has shown a great promise as a solution to the high demand for tissue and organ transplantations. Biomaterial scaffolds serve to house and direct cells to grow, exposing them to an adequate perfusion of nutrients, oxygen, metabolic products, and appropriate growth factors to enhance their differentiation and function. The degradation of biomaterial scaffolds is a key factor to successful tissue regeneration. In this article, the existing degradation control approaches in the context of scaffold tissue engineering were reviewed and a new paradigm of thinking called active control of scaffold degradation, proposed elsewhere by us, was also revisited and discussed in light of its benefit and requirement of this new technology.
We report the discovery and initial characterization of the T-superfamily of conotoxins. Eight different T-superfamily peptides from five Conus species were identified; they share a consensus signal sequence, and a conserved arrangement of cysteine residues (--CC--CC-). T-superfamily peptides were found expressed in venom ducts of all major feeding types of Conus; the results suggest that the T-superfamily will be a large and diverse group of peptides, widely distributed in the 500 different Conus species. These peptides are likely to be functionally diverse; although the peptides are small (11-17 amino acids), their sequences are strikingly divergent, with different peptides of the superfamily exhibiting varying extents of post-translational modification. Of the three peptides tested for in vivo biological activity, only one was active on mice but all three had effects on fish. The peptides that have been extensively characterized are as follows: p5a, GCCP-KQMRCCTL*; tx5a, ␥CC␥DGW ؉ CCT § AAO; and au5a, FC-CPFIRYCCW (where ␥ ؍ ␥-carboxyglutamate, W ؉ ؍ bromotryptophan, O ؍ hydroxyproline, T § ؍ glycosylated threonine, and * ؍ COOH-terminal amidation). We also demonstrate that the precursor of tx5a contains a functional ␥-carboxylation recognition signal in the ؊1 to ؊20 propeptide region, consistent with the presence of ␥-carboxyglutamate residues in this peptide.Cone snails (genus Conus) are perhaps the most successful genus of marine invertebrates, with over 500 species, all of which are venomous (1, 2). These predatory marine snails have evolved a highly sophisticated neuropharmacological strategy based on small peptides (10 -35 amino acids) in their venoms (3, 4). Most Conus peptides potently affect ion channel function; these are widely used pharmacological reagents in neuroscience, and several are being directly developed as diagnostic and therapeutic agents. Most Conus peptides are highly disulfide-rich; generically, Conus peptides with multiple disulfide cross-links have been referred to as conotoxins. It has become apparent in recent years that there are tens of thousands of different conotoxins in Conus venoms. Because of the remarkably rapid interspecific divergence of peptide sequences, each Conus species has its own distinct repertoire of between 50 and 200 different venom peptides (5).A major simplification in understanding this complex array of Conus venom peptides is that most of the ϳ50,000 different molecular forms can be grouped into just a few superfamilies. Peptides in the same superfamily share both a conserved pattern of disulfide connectivity and a highly conserved signal sequence (when prepropeptide precursor sequences of the peptides are compared) (5, 6). Three large superfamilies of conotoxins are well characterized: the O-superfamily, comprising several distinct pharmacological families including the -, -, ␦-, and O-conotoxins (7); the A-superfamily, to which the ␣-conotoxins belong (8); and the M-superfamily, to which the -conotoxins belong. In this paper, we describe the ...
In this work, a nanogenerator-controlled drug delivery system (DDS) for use in cancer therapy is successfully established. A new magnet triboelectric nanogenerator (MTENG) is fabricated that can guarantee the contact and detach cycle between the two friction layers and effectively increase the TENG output, up to 70 V after implantation. Using a special structural design, without the commonly used spacer, this contacting-mode MTENG can ensure a high and consistent electricity output after encapsulation and implantation. Doxorubicin-(DOX-) loaded red blood cells (RBCs) are employed as the anti-tumor DDS in this study. After DOX loading, the RBC membranes are stable and the self-release is very slow. However, upon electric stimulation from the MTENG, the release of DOX is remarkably increased, and falls back to normal again after the stimulation. Thus a controllable DDS is established. The MTENG-controllable DDS achieves an outstanding killing of carcinomatous cells both in vitro and in vivo at a low DOX dosage. These results demonstrate a prominent therapeutic effect of the MTENGcontrolled DDS for cancer therapy, which is highly promising for application in the clinic.
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